Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol ACSL4 contributors: mct - updated : 06-10-2017
HGNC name acyl-CoA synthetase long-chain family member 4
HGNC id 3571
DNA
TYPE functioning gene
STRUCTURE 92.07 kb     17 Exon(s)
regulatory sequence Promoter (CAAT box)
Binding site   transcription factor
text structure
  • transcription factor binding sites for AP2, AP4 and CREB
  • likely absence of a TATA box and the presence of many putative binding sites for transcription factors including Sp1 and CREB
    • MAPPING cloned Y linked N status confirmed
    regionally located between WI-17685 and CHLC. GATA81B07
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 splicing 5039 74.4 670 . expressed in human arterial smooth muscle cells (SMCs) . localized to the inner side of the plasma membrane including microvilli, and was also present in the cytosol 2014 24201376
  • ACSL4 v1
  • being 97p100 identical to the rat homolog
    • 17 splicing 5351 79.2 711 highly expressed in the brain 2014 24201376
  • not found in rat
  • a 41 aa longer hydrophobic N terminus which may impact localization
  • containing an additional 313nt 5' exon introducing an earlier inframe start codon
    • 16 - 5058 74.4 670 - 2014 24201376
    16 - 5349 79.2 711 contains an additional N-terminal hydrophobic region; this isoform was located at the endoplasmic reticulum and on lipid droplets 2014 24201376
    ACSL4v2
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly Homo sapiens
    Endocrinepancreas     Homo sapiens
    Nervousbrain   specific Homo sapiens
    Respiratorylung   moderately Homo sapiens
    Urinarykidney   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Nervouscentral  specific Homo sapiens
    Nervousperipherous  specific Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiens
    Lymphoid/Immunelymphocyte
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two domains of homology with click beetle luciferase, enzyme containing 25-AA consensus sequence, (FACs signature motif)
  • a N terminal insertion sequence in transcripts from brain and retina
    • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to murine Facl4
    homolog to C.elegans F37C12.
    intraspecies
    Homologene
    FAMILY
  • long-chain fatty-acid-coenzyme A ligase family
  • ATP-dependent AMP-binding enzyme family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,peroxisome
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,microsome
    basic FUNCTION
  • converting free long-chain fatty acids into fatty acyl-CoA esters
  • playing a role in lipid biosynthesis and fatty acid degradation
  • utilizing preferentially arachidonate and eicosapentaenoate as substrat
  • might play a role in the growth of hepatic cancer cells
  • involved in learning and memory
  • its expression controls both lipooxygenase and cyclooxygenase metabolism of arachidonic acid
  • modulates PGE&
    • 8322; release from human smooth muscle cells and may regulate a number of processes dependent on the release of arachidonic acid-derived lipid mediators in the arterial wall
  • plays crucial roles in physiological functions such as steroid synthesis and in pathological processes such as tumorigenesis
  • specifically expressed in brain and playing an important role in arachidonate metabolism and neuronal differentiation in the brain
  • might play a key role in brain function, especially neuronal cells
  • might play an important role during neuronal differentiation at the early phase
  • key enzyme in steroidogenesis
  • phosphoprotein whose phosphorylation is hormone-dependent
  • acts as a dimer and phosphorylation occurs after dimer formation
  • is involved in several cellular functions including steroidogenesis, synaptic development and cancer metastasis
  • is required for ferroptotic cancer cell death, and is not only a sensitive monitor of ferroptosis, but also an important contributor of ferroptosis
  • ACSL4 is an essential component for ferroptosis execution
  • involvement of ACSL4 and ACSL3 in insulin secretion
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text mental development
    PATHWAY
    metabolism lipid/lipoprotein
    signaling
    lipid metabolism
    a component protein complex consisting HTATIP2, SH3GLB1, and ACSL4 that interacts with RAB5a and regulates EGFR endocytosis and signaling
    INTERACTION
    DNA
    RNA
    small molecule metal binding, cofactor, nucleotide,
  • magnesium Mg2+
  • AMP
    • protein
  • interaction with PTPN11 (involvement of PTPN11 activity in the regulation of the expression of the fatty acid-metabolizing enzyme ACSL4)
  • PPARD-mediated regulatory mechanism for ACSL4 expression in liver tissue and cultured hepatic cells
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) MRX68 , MRX63 , AMME
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast cancer, colon and hepatocellular carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    new potential therapeutic target for Hepatocellular Carcinoma as an independent adverse prognostic parameter
    cancer  
    ACSL4 inhibition is a viable therapeutic approach to preventing ferroptosis-related diseases
    ANIMAL & CELL MODELS
    mice heterozygocis for Facl4 deficiency (Cho, 2001)